Entry #: 23
Date: 25 November 2017
Topic: Oleacein and anti-inflammatory effects
Type: Original Paper
Expert review of literature related to olives and olive oil
D. Elizabeth McCord, Nancy B. Ray and Tom C. Karagiannis
Oleacein enhances anti-inflammatory activity of human macrophages by increasing CD163 receptor expression
Filipek et al
Citation / Year
(1) / 2015
Oleacein, inflammation, macrophages, CD163 receptor, interleukin-10, haemoglobin, haptoglobin, heme oxygenase 1
The olive bioactive secoiridoid, oleacein (dialdehydic form of elenolic acid linked to hydroxytyrosol), derived from the abundant olive phenolic, oleuropein is gaining much recent attention as a potent anti-inflammatory agent. For example, a recent ex vivo study highlighted the inhibition of human carotid plaque destabilization by the compound (2). To date, oleacein has not as been as thoroughly investigated compare to other olive phenolics particularly, oleuropein, tyrosol, hydroxytyrosol and oleocanthal. Nevertheless, apart from the recent ex vivo study (2), evidence for anti-atherosclerotic effects have been accumulating via a series of in vitro studies. For example, it has been shown that oleacein, attenuates hydrogen peroxide-induced DNA damage in monocytes (3), prevents the increase of expression of the proinflammatory CD11b/18 on neutrophils (4), and reduces monocyte adhesion to human umbilical vein endothelial cells, via inhibition of the expression of the adhesion molecules VCAM-1, ICAM-1, and E-selectin (5). Further it has been shown that via increased expression of heme oxygenase 1, oleacein protects from the pathogenic effects of angiotensin II in endothelial progenitor cells (6). Using a cell culture model, the aim of this study was to investigate the anti-inflammatory effects of oleacein in isolated human macrophages.
Key points and implications
This study focussed on the expression levels of the cysteine-rich scavenger receptor CD163, interleukin-10 and heme oxygenase-1, all of which have implications in the pathogenesis of atherosclerotic plaques. Free haemoglobin (Hb) released from red blood cells exhibits oxidative toxic effects and binding of free Hb by haptoglobin (Hp) forming a HbHp complex provides a critical defence mechanism (7). Unlike free Hb or HP, these HbHp complexes bind with high affinity to CD163 receptors and are scavenged by macrophages resulting in an anti-inflammatory effect (7). Further it has been that the anti-inflammatory cytokine interleukin-10 enhances the expression of the CD163 expression on macrophages (8, 9). Similarly, the heme oxygenase-1 enzyme is a key antioxidant protein that degrades free heme implicated with the CD163 pathway (10). This provides the basis for the current study which indicated that oleacein (10 and 20 μM up to five days), in the presence of HbHp complexes had a profound effect, increasing the expression of the CD163 receptor (30-100-fold) and interleukin-10 (170-300-fold) accompanied by an increase in mRNA levels for CD163 (up to 48 hours), and enhancing the secretion heme-oxygenase-1 in human macrophages. Overall, these important findings provide a molecular basis for the anti-inflammatory effects of oleacein, which may be unique compared to other more well-investigated olive phenolics.
- A. Filipek, M. E. Czerwinska, A. K. Kiss, M. Wrzosek, M. Naruszewicz, Oleacein enhances anti-inflammatory activity of human macrophages by increasing CD163 receptor expression. Phytomedicine : international journal of phytotherapy and phytopharmacology 22, 1255-1261 (2015).
- A. Filipek, M. E. Czerwinska, A. K. Kiss, J. A. Polanski, M. Naruszewicz, Oleacein may inhibit destabilization of carotid plaques from hypertensive patients. Impact on high mobility group protein-1. Phytomedicine : international journal of phytotherapy and phytopharmacology 32, 68-73 (2017).
- R. Fabiani et al., Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and HL60 cells. The Journal of nutrition 138, 1411-1416 (2008).
- M. E. Czerwinska, S. Granica, A. K. Kiss, Effects of an aqueous extract from leaves of Ligustrum vulgare on mediators of inflammation in a human neutrophils model. Planta medica 79, 924-932 (2013).
- G. Sindona et al., Anti-inflammatory effect of 3,4-DHPEA-EDA [2-(3,4 -hydroxyphenyl) ethyl (3S, 4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate] on primary human vascular endothelial cells. Current medicinal chemistry 19, 4006-4013 (2012).
- A. Parzonko, M. E. Czerwinska, A. K. Kiss, M. Naruszewicz, Oleuropein and oleacein may restore biological functions of endothelial progenitor cells impaired by angiotensin II via activation of Nrf2/heme oxygenase-1 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 20, 1088-1094 (2013).
- B. O. Fabriek, C. D. Dijkstra, T. K. van den Berg, The macrophage scavenger receptor CD163. Immunobiology 210, 153-160 (2005).
- D. J. Schaer et al., CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin. Blood 107, 373-380 (2006).
- J. H. Graversen, M. Madsen, S. K. Moestrup, CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma. The international journal of biochemistry & cell biology 34, 309-314 (2002).
- P. Philippidis et al., Hemoglobin scavenger receptor CD163 mediates interleukin-10 release and heme oxygenase-1 synthesis: antiinflammatory monocyte-macrophage responses in vitro, in resolving skin blisters in vivo, and after cardiopulmonary bypass surgery. Circulation research 94, 119-126 (2004).